Long-term Safety of Vedolizumab for Inflammatory Bowel Disease in Children

No longer recruiting at 63 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Pregnancy, Heart failure, PML, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: Up to approximately 8 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of vedolizumab (Entyvio) in children with inflammatory bowel diseases, specifically ulcerative colitis (UC) and Crohn’s disease (CD). Vedolizumab is administered through an IV drip, with participants divided into two groups: one receiving a higher dose and the other a lower dose. The trial targets children who have UC or CD and demonstrated improvement in a previous study. Participants must have completed the prior study with signs of improvement. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Will I have to stop taking my current medications?

You may continue taking certain medications like oral 5-aminosalicylic acid, corticosteroids, probiotics, antidiarrheals, specific antibiotics, azathioprine, 6-mercaptopurine, or methotrexate if you were already on them during a previous study. The trial does not specify stopping other medications, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vedolizumab is generally safe for children with inflammatory bowel disease (IBD). Studies have found that it helps maintain long-term symptom relief in children with ulcerative colitis (UC) and Crohn's disease (CD). One study noted that vedolizumab was effective even for those who had tried other treatments without success, reporting very few safety concerns.

Another review found that vedolizumab was more successful in children with UC compared to those with CD. Importantly, only a few side effects were reported, suggesting that vedolizumab is generally well-tolerated in children. However, vedolizumab is not officially approved for use in children, even though it is used safely in adults. Always consult a healthcare professional about the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Vedolizumab is unique because it specifically targets the gut, acting on a molecule called integrin α4β7, which helps control inflammation in the digestive tract. Unlike other treatments for inflammatory bowel disease (IBD), such as steroids or immunosuppressants that can affect the entire immune system, vedolizumab's targeted approach may reduce side effects and improve safety, especially for children. Researchers are excited about vedolizumab because its potential for a more focused action might lead to better long-term outcomes and quality of life for young patients with ulcerative colitis (UC) or Crohn's disease (CD).

What evidence suggests that vedolizumab might be an effective treatment for inflammatory bowel disease in children?

Studies have shown that vedolizumab effectively treats inflammatory bowel disease (IBD) in children. One study found that about 43% of children had no symptoms and didn't need corticosteroids after a year of treatment. Another study found that vedolizumab helped many children, especially those with ulcerative colitis, feel better within 14 weeks. In this trial, researchers will assign participants to either a high-dose or low-dose group of vedolizumab to assess its long-term safety. The treatment has been considered safe for long-term use, with ongoing therapy providing good results. Overall, vedolizumab appears promising for managing IBD in young patients. ^{5 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for children and teens aged 2-17 with Ulcerative Colitis or Crohn's Disease who have previously responded to Vedolizumab treatment. They must be up-to-date on vaccinations, may use certain antibiotics, and can continue in the study after turning 18 if eligible. Pregnant or lactating females, those with serious health issues, or allergies to Vedolizumab cannot participate.

Inclusion Criteria

I completed Study MLN0002-2003 and met its success criteria.

I was between 2 to 17 years old when I joined the MLN0002-2003 study for UC or CD.

I am currently taking medication for my condition.

Exclusion Criteria

I am currently pregnant or breastfeeding.

I have symptoms that may suggest brain infection before starting the study drug.

I might need major surgery for my ulcerative colitis or Crohn's disease during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vedolizumab IV infusion every 8 weeks, with dose adjustments based on disease progression

Up to approximately 8 years

Every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving vedolizumab IV until it is commercially available or other drug access programs become available

Up to approximately 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Vedolizumab

Trial Overview The trial is testing the long-term safety of an IV medication called Vedolizumab in young patients with inflammatory bowel diseases like UC and CD. It aims to understand how safe it is when used over a longer period.

How Is the Trial Designed?

Group I: Vedolizumab Low Dose Group Experimental Treatment 1 Intervention

Participants with UC or CD having baseline weight of \>= 30 kg will receive vedolizumab 150 mg and participants with UC or CD having baseline weight of \< 30 kg will receive vedolizumab 100 mg IV infusion, every 8 weeks until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug (up to approximately 8 years).

Group II: Vedolizumab High Dose Group Experimental Treatment 1 Intervention

Participants with UC or CD having baseline weight of greater than or equal to (\>=) 30 kilogram (kg) will receive vedolizumab 300 mg and participants with UC or CD having baseline weight of less than (\<) 30 kg will receive vedolizumab 200 mg, IV infusion, every 8 weeks until vedolizumab IV is commercially available for pediatric indication(s) in the participant's country or until other drug access programs become available (whichever comes first), the participant turns 18 years of age and can be transitioned to commercial drug (up to approximately 8 years).

Vedolizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in United States as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Canada as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Approved in Japan as Entyvio for:

• Ulcerative colitis
• Crohn's disease

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

Vedolizumab is a monoclonal antibody that effectively targets the α4β7 integrin to inhibit gut lymphocyte trafficking, providing a safe treatment option for patients with moderate to severe Crohn's disease and ulcerative colitis.

Unlike anti-TNF agents, which some patients may become intolerant to or lose response over time, vedolizumab offers a promising alternative for those who are primary nonresponders or have developed antidrug antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis. Ha, C., Kornbluth, A.[2022]

Vedolizumab is an effective treatment for moderate-to-severe inflammatory bowel diseases like Crohn's disease and ulcerative colitis, with a well-established safety profile based on extensive clinical trial data and real-world studies.

The safety data indicates no unexpected long-term risks, making vedolizumab a strong candidate for combination therapies in patients with complex or refractory cases of inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of long-term vedolizumab use in inflammatory bowel disease. Honap, S., Netter, P., Danese, S., et al.[2023]

In patients treated with vedolizumab, the incidence of opportunistic infections was low, at 0.7 per 100 patient-years in clinical trials and 1.0 in long-term safety studies, indicating a favorable safety profile for this medication.

No cases of serious infections like progressive multifocal leukoencephalopathy or hepatitis B/C viral reactivation were reported, and most patients continued treatment without significant issues, suggesting vedolizumab is a safe option for managing inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting. Ng, SC., Hilmi, IN., Blake, A., et al.[2023]

Vedolizumab is a humanized monoclonal antibody that targets the α4β7 integrin receptor, specifically designed for treating moderate-to-severe ulcerative colitis and Crohn's disease in adults who have not responded well to standard therapies.

It has received global approval, including in the US and EU, for patients who have had inadequate responses to other treatments, highlighting its role as an important option for those with difficult-to-treat inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: first global approval. Poole, RM.[2021]

In phase III clinical trials, vedolizumab significantly improved clinical response and remission rates in patients with ulcerative colitis compared to placebo at both 6 and 52 weeks, demonstrating its efficacy for this condition.

While vedolizumab showed mixed results for Crohn's disease, it was effective in achieving clinical remission at 52 weeks in maintenance treatment, and it is generally well tolerated, with a lower risk of serious side effects compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease. Garnock-Jones, KP.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36306803/

Outcomes, dosing, and predictors of vedolizumab ... Interpretation: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36776669/

Vedolizumab Experience in Children and Adolescents With ... Vedolizumab was safe and effective in this pediatric population with approximately 43% achieving CS-free clinical remission at 1 year.

3. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(24)00319-4/abstract

54-week outcomes of a multicentre, prospective, cohort study Vedolizumab maintenance seems safe and efficacious in children, with a higher efficacy in those with ulcerative colitis than in those with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07198113

COMPARE - Pediatric Inflammatory Bowel Disease (PIBD) The purpose of the study is to compare the clinical effectiveness and safety of newer inflammatory bowel disease (IBD) medications in ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125322003077

Articles Outcomes, dosing, and predictors of vedolizumab ... Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8978350/

Efficacy and safety of vedolizumab for pediatrics with ... We conducted a systematic review evaluating the efficacy and safety of vedolizumab in children and adolescents with inflammatory bowel disease (IBD).

7. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i94/7967054

DOP006 Long term maintenance treatment with vedolizumab ... Vedolizumab was safe and effective for maintaining long-term remission in children with UC and CD. Remission rates were higher in UC compared to ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14740338.2023.2247976

An update on the safety of long-term vedolizumab use in ... 5.2.​​ Vedolizumab is a safe and effective therapy for adult IBD patients, but its use in pediatric patients remains off-label despite receiving regulatory ...

9. journals.lww.com journals.lww.com/ajg/abstract/2019/10001/1147_long_term_efficacy_of_vedolizumab_in.1147.aspx

1147 Long-Term Efficacy of Vedolizumab in Pediatric... Our data suggest that VDZ is effective in achieving clinical remission in pediatric IBD pts with prior anti-TNF failure, with minimal safety concerns. We ...